of 15 IU/ml the fetus could be severely anaemic and therefore cordocentesis should be considered. >
1 Nicolaides KH, Soothill PW, Clewell WH, Rodeck CH, Mibashan R, Campbell S. Fetal haemoglogin measurement in the assessment of red cell isoimmunisation. Lancet 1988;i: 1073-5. 2 Rodeck CH, Nicolaides KH, Warsof SL, Fysh WJ, Gamsu HR, Kemp JR. The management of severe rhesus isoimmunisation by fetoscopic intravascular transfusions. Amj Obstet Gynecol 1984;150:769-74.
3 Nicolaides KH, Soothill PW, Rodeck CH, Clewell W. Rh disease: intravascular fetal blood transfusion by cordocentesis. Fetal Therapy 1986;1: 185-92. 4 Marsh WL, Nichols M, Jenkins WJ. Automated detection of blood group antibodies. Journal of Medical and Laboratory Technology 1968;25:335-42. 5 Nicolini U, Kochenour NK, Greco P, Letsky EA, Johnson RD, Contreras M, et al. Consequences of fetomaternal haemorrhage after intrauterine transfusion. BMJ7 1988;297:1379-81. (Accepted 13Januarv 1992)
Inhaled atrial natriuretic peptide and asthmatic airways
Placebo 0.1 mg atrial natriuretic peptide - * 1 mg atrial natriuretic peptide
*------
0.0
Geoffrey Hulks, Neil C Thomson Department of Respiratory Medicine, Western Infirmary, Glasgow GIl 6NT Geoffrey Hulks, Wellcome Research Fellow Neil C Thomson, consultant physician
Correspondence to: Dr G Hulks, Department of Respiratory Medicine, City Hospital, Edinburgh EH10 5SB. BMJ 1992;304:1156
Pathophysiological plasma concentrations of atrial natriuretic peptide have been shown to have a bronchodilator effect in constricted asthmatic airways,' 2 and lower doses may decrease bronchial hyperresponsiveness,3 a hallmark of asthma. This observation is of considerable interest as animal models suggest that the intracellular action of atrial natriuretic peptide in the airway is mediated by cyclic GMP,4 whereas fi agonists, which are the current first line bronchodilator treatment for asthma, act through cyclic AMP. Drugs for treating airway diseases are best given directly into the airway itself, and the purpose of this study was to ascertain any bronchoprotective effect of inhaled atrial natriuretic peptide.
Subjects, methods, and results We studied eight subjects (three women) with atopic asthma. Their mean forced expiratory volume in one second (FEV1) was 94% (SD 8%) of the predicted value. All subjects showed at least moderate bronchial hyperreactivity to inhaled histamine-that is, histamine at a concentration of s,2 mg/ml, produced ¢20% fall in FEVI. On three separate days subjects received either nebulised atrial natriuretic peptide (0 1 mg or 1 mg) or placebo in a double blind, randomised manner. FEV1 was tested at 30, 90, and 180 seconds after inhalation and immediately thereafter a single two minute inhalation of histamine was given in a dose extrapolated from the screening visit to produce a 25% fall in FEV, . FEV1 was measured again at 30, 90, and 180 seconds and repeated at 5, 10, 15, and 20 minutes. Forced expiratory volumes at baseline and after atrial natriuretic peptide were compared by analysis of variance. There was no significant variation in baseline FEV1 between study days nor was there any significant change in FEV1 after atrial natriuretic peptide alone. All subjects showed a pronounced inhibition of histamine induced bronchospasm with 1 mg atrial natriuretic peptide (figure). The maximum fall in FEV1 was 26 8 (SE 0-7)% with placebo, 22-6 (3-3)% with 0 1 mg atrial natriuretic peptide, and 9 2 (2 2)% with 1 mg (p
1 Nicolaides KH, Soothill PW, Clewell WH, Rodeck CH, Mibashan R, Campbell S. Fetal haemoglogin measurement in the assessment of red cell isoimmunisation. Lancet 1988;i: 1073-5. 2 Rodeck CH, Nicolaides KH, Warsof SL, Fysh WJ, Gamsu HR, Kemp JR. The management of severe rhesus isoimmunisation by fetoscopic intravascular transfusions. Amj Obstet Gynecol 1984;150:769-74.
3 Nicolaides KH, Soothill PW, Rodeck CH, Clewell W. Rh disease: intravascular fetal blood transfusion by cordocentesis. Fetal Therapy 1986;1: 185-92. 4 Marsh WL, Nichols M, Jenkins WJ. Automated detection of blood group antibodies. Journal of Medical and Laboratory Technology 1968;25:335-42. 5 Nicolini U, Kochenour NK, Greco P, Letsky EA, Johnson RD, Contreras M, et al. Consequences of fetomaternal haemorrhage after intrauterine transfusion. BMJ7 1988;297:1379-81. (Accepted 13Januarv 1992)
Inhaled atrial natriuretic peptide and asthmatic airways
Placebo 0.1 mg atrial natriuretic peptide - * 1 mg atrial natriuretic peptide
*------
0.0
Geoffrey Hulks, Neil C Thomson Department of Respiratory Medicine, Western Infirmary, Glasgow GIl 6NT Geoffrey Hulks, Wellcome Research Fellow Neil C Thomson, consultant physician
Correspondence to: Dr G Hulks, Department of Respiratory Medicine, City Hospital, Edinburgh EH10 5SB. BMJ 1992;304:1156
Pathophysiological plasma concentrations of atrial natriuretic peptide have been shown to have a bronchodilator effect in constricted asthmatic airways,' 2 and lower doses may decrease bronchial hyperresponsiveness,3 a hallmark of asthma. This observation is of considerable interest as animal models suggest that the intracellular action of atrial natriuretic peptide in the airway is mediated by cyclic GMP,4 whereas fi agonists, which are the current first line bronchodilator treatment for asthma, act through cyclic AMP. Drugs for treating airway diseases are best given directly into the airway itself, and the purpose of this study was to ascertain any bronchoprotective effect of inhaled atrial natriuretic peptide.
Subjects, methods, and results We studied eight subjects (three women) with atopic asthma. Their mean forced expiratory volume in one second (FEV1) was 94% (SD 8%) of the predicted value. All subjects showed at least moderate bronchial hyperreactivity to inhaled histamine-that is, histamine at a concentration of s,2 mg/ml, produced ¢20% fall in FEVI. On three separate days subjects received either nebulised atrial natriuretic peptide (0 1 mg or 1 mg) or placebo in a double blind, randomised manner. FEV1 was tested at 30, 90, and 180 seconds after inhalation and immediately thereafter a single two minute inhalation of histamine was given in a dose extrapolated from the screening visit to produce a 25% fall in FEV, . FEV1 was measured again at 30, 90, and 180 seconds and repeated at 5, 10, 15, and 20 minutes. Forced expiratory volumes at baseline and after atrial natriuretic peptide were compared by analysis of variance. There was no significant variation in baseline FEV1 between study days nor was there any significant change in FEV1 after atrial natriuretic peptide alone. All subjects showed a pronounced inhibition of histamine induced bronchospasm with 1 mg atrial natriuretic peptide (figure). The maximum fall in FEV1 was 26 8 (SE 0-7)% with placebo, 22-6 (3-3)% with 0 1 mg atrial natriuretic peptide, and 9 2 (2 2)% with 1 mg (p
